Chlorotrifluoroethylcysteine Interaction with Rabbit Proximal Tubule Cell Basolateral Membrane Organic Anion Transport and Apical Membrane Amino Acid Transport

• Published in: The Journal of pharmacology and experimental therapeutics 1999-11, Vol.291 (2), p.555-561
• Main Authors: Groves, C E, Morales, M N
• Format: Article
• Language: English
• Subjects: Amino Acids - pharmacokinetics; Animals; Anions - pharmacokinetics; Biological Transport, Active - drug effects; Cell Membrane - drug effects; Cells, Cultured; Contrast Media - pharmacokinetics; Cysteine - analogs & derivatives; Cysteine - pharmacology; Epithelium - drug effects; Epithelium - metabolism; Female; Fluorescein - pharmacokinetics; Kidney Tubules, Proximal - drug effects; Male; p-Aminohippuric Acid - pharmacokinetics; Phenylalanine - pharmacology; Rabbits; Time Factors
• ISSN: 0022-3565; 1521-0103

The interaction of the cysteine conjugate S -(1-chloro-1,2,2,-trifluoroethyl)- l -cysteine (CTFC) with organic anion and amino acid transport in the basolateral and apical membranes was examined with rabbit renal proximal tubule suspensions and primary cultures of rabbit renal proximal tubule cells. The apparent K i for CTFC inhibition of the 1-min uptake of [ 3 H] p -aminohippurate in tubule suspensions was 105 ± 3 μM and suggests that CTFC interacts with basolateral organic anion transport. Also, the addition of 1 mM CTFC decreased the secretion and intracellular accumulation of fluorescein by ∼70 to 75%. The addition of 1 mM CTFC to the apical compartment decreased the reabsorption and intracellular accumulation of the amino acid [ 3 H]phenylalanine by ∼60 to 70%. Similar to CTFC, saturating concentrations of the organic anion [ 3 H] p -aminohippurate and the amino acid phenylalanine reduced by ∼75% fluorescein secretion and [ 3 H]phenylalanine reabsorption, respectively, by ∼60 to 70%. Thus, the cysteine conjugate CTFC appears to be a potent inhibitor of basolateral organic anion and apical amino acid transepithelial transport. In contrast to its effects on apical phenylalanine uptake, CTFC had no effect on the basal uptake of [ 3 H]phenylalanine by primary cultures. The presence of CTFC in the external bath did trans -stimulate the efflux of fluorescein and [ 3 H]phenylalanine across the basal and apical membrane in tubule suspensions or primary cultures, respectively, grown on plastic. Collectively, these data demonstrate that CTFC interacts with, and is transported by, two anatomically and functionally distinct transporters, the basolateral organic anion and apical neutral amino acid pathways, in the rabbit renal proximal tubule cell.